Plugged tip delivery tube for marker placement

ABSTRACT

The invention provides marker delivery devices, assemblies, and methods. Assemblies embodying features of the invention include marker delivery devices having a delivery tube with an orifice, markers, and a plug releasably disposed in the tube occluding the orifice. The plug prevents markers from passing through the orifice before the marker is to be placed at a desired location within a patient&#39;s body, prevents ingress of tissue into the bore of the tube, and allows markers to pass out of the orifice when marker delivery is desired. Guidance of a delivery tube to a desired location within a patient&#39;s body may include the use of an imaging device, with or without the use of a guide cannula. The plug may itself serve as a marker, and may be the sole marker. Markers may be detectable by ultrasound, X-ray, magnetic resonance imaging, and other imaging devices, and may include bioactive elements.

FIELD OF THE INVENTION

[0001] The invention is directed generally to devices and methods fordelivering markers to a desired location within a patient's body. Inparticular, the invention is directed to devices, assemblies, andmethods configured to retain a biological marker within a deliverydevice before delivery of the marker to a desired intracorporeallocation.

BACKGROUND OF THE INVENTION

[0002] In diagnosing and treating certain medical conditions, it isoften desirable to mark a suspicious body site for the subsequent takingof a biopsy, delivery of medicine, radiation, or other treatment, tomark a location from which a biopsy was taken, or at which some otherprocedure was performed. As is known, obtaining a tissue sample bybiopsy and the subsequent examination are typically employed in thediagnosis of cancers and other malignant tumors, or to confirm that asuspected lesion or tumor is not malignant. The information obtainedfrom these diagnostic tests and/or examinations is frequently used todevise a therapeutic plan for the appropriate surgical procedure orother course of treatment.

[0003] In many instances, the suspicious tissue to be sampled is locatedin a subcutaneous site, such as inside a human breast. To minimizesurgical intrusion into patient's body, it is often desirable to inserta small instrument, such as a biopsy needle, into the body forextracting the biopsy specimen while imaging the procedure usingfluoroscopy, ultrasonic imaging, x-rays, magnetic resonance imaging(MRI) or any other suitable form of imaging technique. Examination oftissue samples taken by biopsy is of particular significance in thediagnosis and treatment of breast cancer. In the ensuing discussion, thebiopsy and treatment site described will generally be the human breast,although the invention is suitable for marking biopsy sites in otherparts of the human and other mammalian body as well.

[0004] Periodic physical examination of the breasts and mammography areimportant for early detection of potentially cancerous lesions. Inmammography, the breast is compressed between two plates whilespecialized x-ray images are taken. If an abnormal mass in the breast isfound by physical examination or mammography, ultrasound may be used todetermine whether the mass is a solid tumor or a fluid-filled cyst.Solid masses are usually subjected to some type of tissue biopsy todetermine if the mass is cancerous.

[0005] If a solid mass or lesion is large enough to be palpable, atissue specimen can be removed from the mass by a variety of techniques,including but not limited to open surgical biopsy, a technique known asFine Needle Aspiration Biopsy (FNAB) and instruments characterized as“vacuum assisted large core biopsy devices”.

[0006] If a solid mass of the breast is small and non-palpable (e.g.,the type typically discovered through mammography), a biopsy procedureknown as stereotactic needle biopsy may be used. In performing astereotactic needle biopsy of a breast, the patient lies on a specialbiopsy table with her breast compressed between the plates of amammography apparatus and two separate x-rays or digital video views aretaken from two different points of view. A computer calculates the exactposition of the lesion as well as depth of the lesion within the breast.Thereafter, a mechanical stereotactic apparatus is programmed with thecoordinates and depth information calculated by the computer, and suchapparatus is used to precisely advance the biopsy needle into the smalllesion. Depending on the type of biopsy needle(s) used, thisstereotactic technique may be used to obtain cytologic specimens, e.g.,obtained through FNAB or it may be used to obtain histologic specimense.g., obtained through coring needle biopsy. Usually at least fiveseparate biopsy specimens are obtained from locations around the smalllesion as well as one from the center of the lesion.

[0007] The available treatment options for cancerous lesions of thebreast include various degrees of mastectomy or lumpectomy and radiationtherapy, as well as chemotherapy and combinations of these treatments.However, radiographically visible tissue features, originally observedin a mammogram, may be removed, altered or obscured by the biopsyprocedure, and may heal or otherwise become altered following thebiopsy. In order for the surgeon or radiation oncologist to directsurgical or radiation treatment to the precise location of the breastlesion several days or weeks after the biopsy procedure was performed,it is desirable that a biopsy site marker be placed in or on thepatient's body to serve as a landmark for subsequent location of thelesion site. A biopsy site marker may be a permanent marker (e.g., ametal marker visible under X-ray examination), or a temporary marker(e.g., a bioresorbable marker detectable with ultrasound). While currentradiographic type markers may persist at the biopsy site, an additionalmammography generally must be performed at the time of follow uptreatment or surgery in order to locate the site of the previous surgeryor biopsy. In addition, once the site of the previous procedure islocated using mammography, the site must usually be marked with alocation wire which has a hook on the end which is advanced into site ofthe previous procedure. The hook is meant to fix the tip of the locationwire with respect to the site of the previous procedure so that thepatient can then be removed from the confinement of the mammographyapparatus and the follow-up procedure performed. However, as the patientis removed from the mammography apparatus, or otherwise transported theposition of the location wire can change or shift in relation to thesite of the previous procedure. This, in turn, can result in follow-uptreatments being misdirected to an undesired portion of the patient'stissue.

[0008] As an alternative or adjunct to radiographic imaging, ultrasonicimaging and visualization techniques (herein abbreviated as “USI”) canbe used to image the tissue of interest at the site of interest during asurgical or biopsy procedure or follow-up procedure. USI is capable ofproviding precise location and imaging of suspicious tissue, surroundingtissue and biopsy instruments within the patient's body during aprocedure. Such imaging facilitates accurate and controllable removal orsampling of the suspicious tissue so as to minimize trauma tosurrounding healthy tissue.

[0009] For example, during a breast biopsy procedure, the biopsy deviceis often imaged with USI while the device is being inserted into thepatient's breast and activated to remove a sample of suspicious breasttissue. As USI is often used to image tissue during follow-up treatment,it may be desirable to have a marker, similar to the radiographicmarkers discussed above, which can be placed in a patient's body at thesite of a surgical procedure and which are visible using USI. Such amarker enables a follow-up procedure to be performed without the needfor traditional radiographic mammography imaging which, as discussedabove, can be subject to inaccuracies as a result of shifting of thelocation wire as well as being tedious and uncomfortable for thepatient.

[0010] Placement of a marker or multiple markers at a location within apatient's body requires delivery devices capable of holding markerswithin the device until the device is properly situated within a breastor other body location. Accordingly, devices and methods for retainingmarkers within a marker delivery device while allowing their expulsionfrom the devices at desired intracorporeal locations are desired.

SUMMARY OF THE INVENTION

[0011] The invention provides devices and systems for delivery ofmarkers to a site within a patient's body. Delivery systems embodyingfeatures of the invention include a marker delivery tube with aremovable plug. Plugs embodying features of the invention are heldwithin an orifice at the tip of the delivery tube, retaining markerswithin the delivery tube, until it is desired that the markers beejected. The plug may then be ejected or removed from the orifice,allowing the delivery of the markers to a desired site within apatient's body. Plugs and delivery tubes embodying features of theinvention may have retaining features, such as recesses orprotuberances, configured to releasably retain a plug within a deliverytube until ejection of the plug from the delivery tube is desired. Theretaining features are typically complementary pairs, such as a plugprotuberance configured to fit into a recess in the delivery tube.

[0012] Assemblies embodying features of the invention include markerdelivery devices having a delivery tube with an orifice at its distaltip, an inner bore leading to an orifice, and at least one marker(preferably more than one) within the bore of the delivery tube. A plugis disposed at least in part within the bore and orifice to preventmarkers from prematurely passing through the orifice and to preventtissue from entering the bore when the delivery tube is advanced throughtissue. The plug may itself serve as a marker, and may be the solemarker, although typically the delivery tube contains a plug and atleast one other marker. The plug is releasably secured within oradjacent to the orifice in order to retain a marker within the deliverytube bore proximate thereto but to allow passage of the marker out ofthe orifice when the plug is ejected from the orifice. The plug maypartially or completely occlude the orifice, and is configured to retainthe marker within the delivery tube before the marker is to be placed ata desired location within a patient's body, and to allow the marker topass out of the orifice when delivery of the marker is desired. Amovable plunger may be slidably disposed within the tube from an initialposition accommodating the marker or markers and the plug within thetube, to a delivery position to push a marker against the plug to pushthe plug out of the orifice and to then eject one or more markersthrough the orifice.

[0013] The plug is preferably configured to be releasably retainedwithin the delivery tube, and may be aligned in a preferred orientationwithin the delivery tube, to properly orient an inclined face within theorifice. A plug may be configured to fit tightly within a part of thebore of a delivery device so as to be retained by pressure; may have aportion configured to contact a slot, hole, notch, ridge, tab, lip, orother feature of a delivery tube; may be configured to be retained by atab; may include an internal retention element, such as a coil, aspring, a clip, a loop, an arch, or a resilient core, that is configuredto press an outer portion of a plug against a delivery tube wall or tocontact a retaining feature such as a tab, slot, notch or hole; may bepressed against at least part of the bore of a delivery tube by anexternal retention element such as a pin, wedge, clip, spring, coil orother element applied to a plug; or by otherwise engaging a portion of adelivery tube effective to be releasably retained within a deliverytube.

[0014] The plug is preferably biocompatible, and may itself be a markerthat is detectable within a patient's body visually, tactilely, byimaging (including ultrasound, radiographic, magnetic resonance, orother form of imaging), or is otherwise detectable. A plug may be abio-resorbable temporary marker made up of bio-resorbable materials, ormay be a permanent marker including non-bio-resorbable materials aswell. A plug may also include bio-active materials (e.g., hemostaticmaterials, anesthetic materials, absorbent materials, antibioticmaterials, antifungal materials, antiviral materials, chemotherapeuticmaterials, radioactive materials, and other pharmaceutical materials) aswell as biologically inert materials.

[0015] Systems and devices embodying features of the invention may havemarkings or indicators to aid in placement of the delivery tube in adesired location. In addition, methods of using systems and devicesembodying features of the invention include guiding the insertion of thedelivery tube with the aid of an imaging device, such as an ultrasoundimaging device, an x-ray imaging device, and a magnetic resonanceimaging device, which may be used to image the plug, a marker retainedwithin the delivery device, a portion of the delivery device, orcombinations of these.

[0016] The invention provides the advantages of securely retainingmarkers within a marker delivery device, improving accuracy and avoidingerrors in of placement of markers at desired locations within apatient's body, preventing ingress of tissue into the distal tip of thedevice when it is advanced through tissue, and guiding the device by useof an imaging device. These and other advantages of the invention willbecome more apparent from the following description when taken inconjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017]FIG. 1A is a partly cut-away perspective view of a marker deliveryassembly embodying features of the invention showing several markerswithin a marker delivery device and a plug embodying features of theinvention occluding the tip of the delivery device.

[0018]FIG. 1B is a transverse cross-sectional view of the markerdelivery assembly of FIG. 1A taken at line 1B-1B.

[0019]FIG. 1C is a transverse cross-sectional view of the markerdelivery assembly of FIG. 1A taken at line 1C-1C.

[0020]FIG. 1D is a transverse cross-sectional view of the markerdelivery assembly of FIG. 1A taken at line 1D-1D.

[0021] FIGS. 2A-C and 2D-2G are longitudinal cross-sectional views of adelivery tube distal portion embodying features of the inventionconfigured to retain a plug, containing markers and a plug embodyingfeatures of the invention.

[0022]FIG. 2D is a transverse cross-sectional view of the delivery tubedistal portion and plug shown in FIG. 2C.

[0023]FIG. 3A is a longitudinal cross-sectional view of a compressibleplug embodying features of the invention disposed outside a distalportion of a delivery tube.

[0024]FIG. 3B is a longitudinal cross-sectional view of the compressibleplug of FIG. 3A embodying disposed within the distal portion of thedelivery tube.

[0025]FIG. 3C is a longitudinal cross-sectional view of an alternativeembodiment of a compressible plug.

[0026]FIG. 3D is a longitudinal cross-section of a plug containing aninternal retention element configured to press against the wall of adelivery tube.

[0027]FIG. 4A is a longitudinal cross-sectional view of a plug embodyingfeatures of the invention disposed outside a distal portion of adelivery tube.

[0028]FIG. 4B is a longitudinal cross-sectional view of an externalretention element and of a plug embodying features of the inventiondisposed within a distal portion of a delivery tube.

[0029]FIG. 4C is a longitudinal cross-sectional view of the externalretention element inserted into the plug of FIG. 4B embodying disposedwithin the distal portion of the delivery tube.

[0030]FIG. 4D is a perspective view of a sharp tip of a delivery tubedistal portion embodying features of the invention having slits forminga tab configured to retain and align a plug.

[0031]FIG. 4E is a longitudinal cross-section of a delivery tube distalportion embodying features of the invention having a tab configured toretain a plug, and containing a plug configured to be retained andaligned by a tab.

[0032]FIG. 4F is a longitudinal cross-section of a delivery tube distalportion embodying features of the invention having a tab configured toretain and align a plug, and containing a plug configured to be retainedby a tab.

[0033] FIGS. 5A-5H are alternating plan and elevation views of distalportions of delivery tubes of marker delivery devices embodying featuresof the invention configured to retain a plug by having holes or slotsthrough the tube wall.

[0034]FIG. 6 is a partially cut away, perspective view of a human breasthaving a lesion from which a biopsy specimen has been removed, andshowing a guide cannula and a marker delivery assembly embodyingfeatures of the invention inserted into the breast, the assembly havingmarkers and a plug configured to retain the markers within a deliverytube of a delivery device.

DETAILED DESCRIPTION OF THE INVENTION

[0035] Marker delivery assemblies embodying features of the inventionare illustrated in FIGS. 1A-1D. Such assemblies include marker deliverydevices, markers, and a plug occluding a distal portion of the deliverydevice. The assembly 10 shown in FIG. 1A includes a delivery device 12,delivery tube 14 with a bore 16, a distal portion 18, and a proximalportion 20 with a handle 22. Several markers 24, and a plug 26 are showndisposed within the bore 16. A plunger 28 with a plunger handle 30 and aplunger distal end 32 is movable within the tube bore 16, and isconfigured to push markers 24 and plug 26 out of orifice 34 at thedistal tip 36 of delivery tube 14 when the distal end 32 of plunger 28moves in a distal direction. Plunger handle 30 allows an operator toreadily manipulate plunger 28. A device 12 may include a plunger lockingmechanism to prevent inadvertent longitudinal movement of plunger 28;for example, a plunger 28 and a handle 22 may be configured so thatplunger 28 must be rotated some amount before it is able to be moved ina longitudinal direction (by, e.g., having a lateral tab protruding froma portion of the plunger 28 that prevents longitudinal plunger movementuntil the tab is moved to a channel configured to accept it).

[0036] Plug 26 may substantially fill orifice 34, as shown in FIG. 1A,or may occupy or block only a portion of orifice 34. A plug 26preferably does not interfere with the sharp edge of orifice 34 orpointed tip 36 of a delivery tube 14. Where distal tip 36 of deliverytube 14 is sharp, as shown in FIG. 1A, the distal surface 38 of plug 26is preferably configured with an inclined surface to closely follow theconformation of distal tip 36 to provide more effective penetration.

[0037] Markers 24 are preferably configured to slide readily within tubebore 16. Plug 26 is configured to be releasably secured within a portionof tube bore 16, such as a distal portion 18 or orifice 34, effective toprevent inadvertent exit or release of markers 24 from delivery tube 14.The engagement of plug 26 with delivery tube 14 is further configured tobe readily releasable when desired. For example, plug 26 is configuredto release its engagement with delivery tube 14 effective to allow exitof markers 24 upon distal movement of plunger 28. Markers 24 are madewith detectable, biocompatible materials, and may include a radiopaqueelement 40. Plug 26 may be made from the same or similar materials as amarker 24, and may also include a radiopaque element 40.

[0038]FIG. 1B shows a marker delivery device 12 having a delivery tube14 with a distal tip 36 having a notch 42 configured to retain a plug26. A notch 42 is effective to retain a plug 26, particularly if aportion of the plug 26 is formed to engage with the notch 42, or ispressed or otherwise introduced into at least a portion of the notch 42.The delivery tube 14 also has markings 44 which aid in placement of thedevice in a desired location within a patient's body. The markings 44may serve as visual landmarks for guiding an operator in placing thedevice, and may also be radiopaque, ultrasound-reflective, or otherwiseconfigured to be detectable by imaging devices and imaging methods.

[0039] In FIG. 1B, the plug 26 is shown in place within tube bore 16 atthe distal portion 18 of delivery tube 14. In FIG. 1C, a marker 24 withradiopaque element 40 is shown within tube bore 16 of delivery tube 14.In FIG. 1D, a portion the plunger 28 is shown in place within tube bore16 of delivery tube 14.

[0040] FIGS. 2A-2H illustrate several alternative embodiments of a plug26 having features of the invention. The plugs 26 in FIGS. 2A-2C and2E-2H are shown in longitudinal cross-section within a distal portion 18of a delivery tube 14 of a marker delivery device 12 embodying featuresof the invention. FIG. 2A illustrates a plug 26 configured to beretained within a delivery tube 14 and to occlude an orifice 34. Plug 26of FIG. 2A is configured to provide a surface 38 following aconfiguration generally perpendicular to wall 46 conforming to the sharptip 36, effective to aid the penetration of sharp tip 36 into apatient's tissue as well as to retain markers 24 within a deliverydevice 12. A plug 26 embodying features of the invention may be retainedwithin a delivery tube 14 effective to occlude an orifice 34 and toretain a marker 24 in any one or in more than one way. For example, aplug 26 may be retained by friction, adhesion, tension, pressure, orother mechanisms; may be retained mechanically, as by a notch, hole,slot, tab, ridge, lip or other feature of a tube 14, of the plug 26itself, or by any combination of such elements; or by any othermechanism or method suitable to releasably retain a plug while allowingits removal at a desired time. Some examples of such features andelements are illustrated in the figures, although the devices,assemblies and elements embodying features of the invention are notlimited to these examples. Any feature, element, or means of retaining aplug in a location effective to occlude an orifice 34 and to retain amarker 24 within a delivery tube 14, while allowing its removal at adesired time, is suitable for the practice of the invention.

[0041]FIG. 2B illustrates a plug 26 having a protrusion 48 configured toengage a passage 50 through tube wall 46, aiding in the retention ofplug 26 within bore 16 of delivery tube 14. A passage 50 may be a hole,slot, notch, or other void through a tube wall 46. Alternatively, aprotrusion 48 of a plug 26 may engage a slot, notch, or crease along abore 16 that does not completely pass through the wall 46, yet stillprovides purchase for retaining a plug 26 within a delivery tube 14.

[0042]FIG. 2C illustrates a plug 26 embodying features of the inventionhaving a gap 52 allowing compression of plug 26 effective to allowinsertion of plug 26 into distal portion 18, where plug 26 occludesorifice 34. Resilience of plug 26 provides outward pressure followingsuch compression, effective to provide lateral pressure against a wall46 of a delivery tube 14 and so to retain the plug 26 within distalportion 18 of tube 14. The embodiment of a plug 26 illustrated in FIG.2C also has a lip portion 54 effective to limit the extent of insertionof plug 26 into delivery tube 14. It will be understood that a lipportion 54 is optional, and is not present in some plugs 26, includingresilient plugs 26 embodying features of the invention. Preferably, lipportion 54 is configured to leave a sufficient amount of distal tip 36exposed so as to not substantially interfere with penetration of sharptip 36 into the tissue of a patient. For example, a lip portion 54preferably comprises less than a full circumference a plug 26 having around cross-section, and may comprise one or a few extensions 56extending radially outwardly form a plug body 58, as illustrated in FIG.2D in a transverse cross-sectional view of the plug 26 and tube 14 ofFIG. 2C. A plug body 58 may surround a gap 52, as in the plug 26illustrated in FIGS. 2C and 2D, or, in other embodiments, may not have agap 52, as, e.g., in the plugs 26 illustrated in FIGS. 2A and 2B.

[0043] The plug 26 illustrated in FIG. 2E is an irregularly-shaped plug26 embodying features of the invention, configured to occlude an orifice34 and to retain markers 24 within a delivery tube 14 until the plug 26is removed or moved away from its blocking position. Anirregularly-shaped plug 26 may be put into place, for example, by theapplication of a liquid, flexible or pliable material that sets orhardens after placement in or around an orifice 34. Alternatively, amaterial may be placed in or around an orifice 34 and then treated withheat, solvent, hardener, or other treatment in order to fix the plug 26in its final form.

[0044] As illustrated by the embodiment of a plug 26 shown in FIG. 2F,an orifice 34 need not be completely occluded; partial occlusion of anorifice 34 by a plug 26 is sufficient to retain a marker 24 within adelivery tube 14. Such a plug 26 may be retained within the bore 16 of adelivery tube 14 by adhesion or other bonding to a tube wall 46, or by afeature of a tube 14 embodying features of the invention such as a tab,lip, hole, notch, slot, or other retaining element.

[0045] The embodiments of a plug 26 shown in FIGS. 2G and 2H includemarker material effective to mark a location within a patient's body,and thus is configured to act as a marker 24 as well as a plug 26. Forexample, a plug 26 as illustrated in FIGS. 2G and 2H may be a plug 26having a lip portion 54 and a body portion 58 configured to pressagainst a tube wall 46 so as to retain plug 26 within the delivery tube14, and including marker material so as to be able to serve as a marker24 following ejection from orifice 34 and delivery into a desiredlocation within a patient's body. Preferably, a lip portion 54 does notextend so far as to interfere with the cutting action of sharp tip 36. Aplug 26 configured to serve as a marker 24 may include bioresorbablemarker materials, and be a temporary marker, or may includenon-bioresorbable marker materials, and so be a permanent marker. Forexample, the embodiment of a plug 26 shown in FIG. 2H is also configuredto serve as a marker 24, and further includes a radiopaque element 40.Typically, a radiopaque element 40 is a permanent marker element, sothat plug 26 shown in FIG. 2H, for example, may be a permanent marker.

[0046] A compressible plug 26 as illustrated in FIGS. 2C and 2D may beinserted into a delivery tube 14 through an orifice 34 as shown in FIGS.3A and 3B. FIG. 3A shows a longitudinal cross-section of a compressibleplug 26 disposed distal to an orifice 34 of a delivery tube 14.Compression of body 58 effective to reduce the size of gap 52 alsoreduces a lateral dimension of the plug 26 enabling a portion of theplug body 56 to be inserted through orifice 34 into tube bore 16 to bedisposed in position within delivery tube 14 as shown in FIG. 3B.Resiliency of plug body 58 is effective to create pressure against atube wall 46 so as to retain plug 26 in position within bore 16 indistal tube portion 18. In the embodiment shown in FIGS. 3A and 3B, gap52 is disposed so as to face bore 16 of delivery tube 14. Alternatively,as shown in FIG. 3C, a gap 52 may face away from a tube bore 16. Ineither embodiment, plug body 58 is resiliently compressible and snuglyretained within a distal tube portion 18.

[0047] In addition, a further embodiment of a plug 26 embodying featuresof the invention is illustrated in FIG. 3D. A plug 26 may contain aninternal retention element 60 configured to press itself or a portion ofa plug body 58 against a wall 46 of a delivery tube 14. Such an internalretention element 60 may be radiopaque internal retention element 60,and thus, in that case, the plug 26 will also be configured to be aradiopaque marker 24. An internal retention element 60 may be anyelement, including a spring, a coil, a clip, a loop, an arch, aresilient core, or other element that is configured to help retain aplug 26 within a delivery tube 14. For example, a resilient core may bea portion of a plug body 58 which includes a resilient material andwhich provides outward force when a plug 26 is disposed within a bore 16of a delivery tube 14. A plug 26 as illustrated in FIG. 3D is a furtherexample of a compressible plug 26. It will be understood that acompressible plug 26 need not have a gap 52 in order to be resilientlycompressible effective to be inserted into and releasably retainedwithin a delivery tube 14; for example, a plug 26 may be a compressibleplug including an internal retention element 60, or where the entireplug body 58 is formed of a resilient material, such as, for example, afoam or spongy material which tends to re-expand after compression, orwhich tends to resist compression by exerting counteracting forceagainst compression.

[0048] A plug 26 may be releasably retained within a bore 16 of adelivery tube 14 upon addition or insertion of an external retentionelement 62. FIG. 4A illustrates a plug 26 embodying features of theinvention disposed distal to a distal portion 18 of a delivery tube 14.FIG. 4B illustrates the plug 26 of FIG. 4A disposed within distalportion 18, in which plug body 58 does not tightly contact a tube wall46 and plug 26 is not snugly held within delivery tube 14. Also shown inFIG. 4B is an external retention element 62 in the form of a conicalpin. FIG. 4C illustrates a plug 26 embodying features of the inventionincluding external retention element 62 mounted in a gap 52. Followinginsertion of external retention element 62 into plug 26, at least aportion of plug body 58 contacts tube wall 46 effective to releasablyretain plug 26 within a distal portion 18 of delivery tube 14 effectiveto occlude orifice 34 and to retain a marker 24. In other embodiments,an external retention element 62 may be a wedge, a screw, a mandrel, orany other element configured to tend to expand a portion of a plug body58 effective to exert force against a tube wall 46, such as by tendingto expand a plug body 58, or otherwise to aid in retaining a plug 26within a distal portion 18 of a delivery tube 14.

[0049] A delivery tube 14 may be configured to retain and optionally toalign a plug 26. For example, a delivery tube 14 may have a retainingfeature 64, illustrated in FIGS. 4D, 4E and 4F as a tab, configured toengage a plug 26 and to hold it in place. The retaining feature 64 shownin FIG. 4D is a tab of metal formed by two longitudinal slots in thedistal end of the wall 46 of delivery tube 14 that has been deflectedinwardly to engage a plug 26 disposed within the bore 16, as shown inFIGS. 4E and 4F (the tab shown in FIG. 4F may be formed by one radialand two longitudinal slots). A retaining feature 64, such as a tab, mayalso help to align a plug 26 within a delivery tube 14. A plug 26 mayoptionally also be configured to be retained by a retaining feature 64,such as a tab, as illustrated in FIGS. 4E and 4F, although a retainingfeature 64 may be effective to retain a plug 26 without any particularconfiguration of a plug 26. A plug 26 may also be configured to bealigned by a retaining feature 64, e.g., by having a notch, depression,ridge or other feature configured to engage a retaining feature 64.

[0050] Upon expulsion of a plug 26, as may be caused by distal movementof a plunger 28, a retaining feature 64 may become reconfigured to allowpassage of a marker 24 out of an orifice 34 for delivery into a patient.For example, where the retaining feature 64 is a tab intruding into atube bore 16, as shown in FIGS. 4D, 4E and 4F, the expulsion of a plug26 may be effective to bend the tab outwardly so it more closelyapproaches tube wall 46 and does not prevent movement of a marker 24through the bore 16 of a delivery tube 14. Alternatively, a retainingfeature 64 may be unaffected by movement of a plug 26 or a marker 24.For example, a retaining feature 64 may be configured to impede movementof a plug 26 or of a marker 24, without preventing such movement, and soact to releasably retain a plug 26 effective to retain a marker 24within a delivery tube 14 until the delivery of the marker 24 isdesired.

[0051] Several examples of alternative embodiments of retaining features64 are illustrated in FIGS. 5A through 5H, representing some, but notall, suitable types and configurations of retaining features 64embodying features of the invention. A retaining feature 64 may bedisposed at any location on, within, or through a wall 46 of deliverytube 14, although a distal portion 18 of a delivery tube 14 ispreferred. A retaining feature may be continuous with an orifice 34 atthe distal tip 36 of a delivery tube, or may be disposed proximally ofthe distal tip 36 of a delivery tube 14. A delivery tube 14 may includemore than one retaining feature 64, and may include more than one shapeor type of retaining feature 64.

[0052]FIG. 5A is a plan view, and FIG. 5B is an elevation view, of adistal portion 18 of a delivery tube 14 of a marker delivery device 12embodying features of the invention, with a retaining feature 64 that isa rectangular slot 51 through tube wall 46. In FIGS. 5C and 5D, a distalportion 18 of a delivery tube 14 is shown having two retaining features64: a rectangular slot 51 and a round hole 53 through tube wall 46. Thedistal portion 18 of delivery tube 14 shown in FIGS. 5E and 5F hasretaining features 64 that are a round hole 53 and a rectangular slot 51connecting to orifice 34. The retaining features 64 illustrated in FIGS.5G and 5H are all round holes 53 spaced around delivery tube 14.Retaining features 64 may also take other shapes and may be disposed inother positions on a distal portion 18. For example, a retaining featuremay be an irregularly-shaped slot, combining in part a round hole and aslot with angled sides, and may connect with orifice 34 at tube distaltip 36.

[0053] A marker delivery assembly 10 embodying features of the inventionmay be used to deliver a marker 24 to a desired location within apatient's body. Such a desired location is typically a lesion site fromwhich a biopsy sample has been, or is to be, taken, or a lesion has beenor will be removed. Assemblies, devices, and methods embodying featuresof the invention find use, for example, in marking a breast biopsy site.By way of illustration, the use of assemblies, devices and methodsembodying features of the invention will be discussed below in terms ofbreast biopsies and similar uses involving marking sites within a breastof a human female. It will be understood that the assemblies, devicesand methods embodying features of the invention find use in a variety oflocations and in a variety of applications, in addition to the humanbreast.

[0054] An assembly 10 or delivery device 12 can be inserted into abreast 66 through a guide cannula 72, as illustrated in FIG. 6.Alternatively, an assembly 10 or delivery device 12 can be inserteddirectly into a breast 66, using a distal tip 36 that is sharp and so isconfigured to pierce or puncture tissue 68, with or without an initialincision through the skin 70 of a patient. In either case, markings 44along a delivery tube 14 may be used to aid in the proper placement ofthe orifice 34 of a delivery tube 14, and so to aid in the properdelivery of a marker 24 to a desired location within a breast.

[0055] A plug 26 and marker 24 may be introduced into a breast 66 of apatient at a lesion site 74 adjacent or within a biopsy cavity 76, fromwhich a biopsy sample or tissue from a lesion has been taken, asillustrated in FIG. 6. Alternatively, a plug 26 and marker 24 may beintroduced into a patient's body in the absence of a biopsy cavity. Thiscould be useful, for example, to mark a location from which to take abiopsy at a later time. A lesion site 74 may be the site of a suspectedlesion, or a lesion site 74 may be the site of a known lesion. A biopsycavity 76 may be an existing cavity, filled, if at all, with gas orfluid, or may be a virtual cavity, substantially filled with tissue thathas collapsed into, or grown into, a site from which tissue has beenpreviously removed. A biopsy cavity 76 may adjoin, or be lined with, orbe at least in part surrounded by suspicious tissue 78, which may beremaining tissue of a lesion, newly grown tissue at least partiallyfilling a biopsy cavity, tissue injured when the biopsy was taken, orother tissue.

[0056] Assemblies, devices and methods embodying features of theinvention may be used to deliver a marker to a desired location within abody of a patient, by inserting a delivery device 12 into a patienthaving markers 24 retained within the bore 16 of the delivery tube 14 bya plug 26, and expelling a marker 24 from the orifice 34 into thedesired location. A marker 24 may be expelled, for example, bydepressing plunger 28 by moving plunger handle 30. Depression of plunger28, pushing on a marker 24, is preferably effective to expel plug 26from the orifice 34, allowing a marker 24 to exit the delivery tube 14for delivery within a patient.

[0057] An operator may grasp a device handle 22 to guide the device 12during insertion, and to steady the device 12 during depression of theplunger 28. Insertion of a device 12 results in the placement of atleast a portion of the device 12 adjacent a desired location. The device12, in particular the distal tip 36 and orifice 34 of the device 123,may be guided adjacent a desired location such as a lesion site, or abiopsy cavity, or other internal body site where delivery of a marker 24is desired.

[0058] An initial scalpel incision in the skin is typically made inorder to introduce a device 12 into the body tissue of a patient,although in many cases the sharp edge 34 or pointed tip 36 tip may beused to gain access to tissue beneath the skin without the use of anincision by a surgical tool. Insertion of the device 12 into a patient,e.g. into a breast 66 of a patient, may be guided by an operator withthe aid of an imaging device. A delivery tube 14, and/or markings 44, aswell as markers 24 and optionally plug 26, may be detectable by animaging device, such as an ultrasound imaging device, an X-ray imagingdevice, a magnetic resonance imaging device, or other imaging device.Alternatively, or additionally, insertion may be visually guided, or maybe guided by palpation or by other means.

[0059] As illustrated in FIG. 6, insertion of the device 12 into apatient, e.g. into a breast 66 of a patient, may be guided by a guidecannula as well. Such insertion may be performed with or without the aidof an imaging device, such as an ultrasound imaging device, an X-rayimaging device, a magnetic resonance imaging device, or other imagingdevice. Alternatively, or additionally, insertion may be visuallyguided, or may be guided by palpation or by other means.

[0060] A plug 26 may be made with any suitable material. Typically, aplug 26 is made with the same materials as a marker 24. A plug 26 mayserve as a marker after its expulsion from orifice 34 and placement intoa patient's body. Preferably, a plug 26 is made with a biocompatiblematerial, and provides sufficient structural strength as to retain amarker 24 within a delivery tube 14 and, where insertion of a deliverydevice embodying features of the invention is performed without the aidof a guide cannula, a material used in making a plug 26 preferably hassufficient structural strength to withstand the forces encounteredduring insertion into tissue or through skin. Materials suitable for usein making a plug 26 embodying features of the invention includepolymers, plastics, resins, waxes, glasses, ceramics, metals, metaloxides, and composites, combinations and mixtures of these materials.For example, a wax such as bone wax, or other biocompatible material issuitable for use in making a plug 26. In presently preferredembodiments, a plug 26 is made with bioresorbable polymers such aspoly-lactic acid and poly-glycolic acid. A plug may be made of more thanone material, as illustrated, for example, in FIG. 3D, showing a plug26, which may be made primarily with a plastic or a polymer, and havingan internal retention element 60, which may be, for example, a metalclip or spring.

[0061] A marker 24, including a plug 26 when configured to also serve asa marker 24, is preferably readily visible by ultrasonic imaging (USI),or by conventional imaging methods, such as x-ray and magnetic resonanceimaging methods, or by more than one imaging technique. Suitablebio-compatible materials which may be used in a marker 24 or a plug 26include polyethylene, polytetrafluoroethylene, PEBAX (made by AutochemCorp.), and the like.

[0062] Thus, biocompatible plugs 26 or markers 24 embodying features ofthe invention are preferably made using materials including abioresorbable material. Some particularly suitable bioresorbablematerials include bio-resorbable polymers including, but not limited to,polymers of lactic acid, glycolic acid, caprolactones, and othermonomers; thus, for example, suitable bio-resorbable polymers mayinclude poly(esters), poly(hydroxy acids), poly(lactones), poly(amides),poly(ester-amides), poly(amino acids), poly(anhydrides),poly(ortho-esters), poly(carbonates), poly(phosphazines),poly(thioesters), poly(urethanes), poly(ester urethanes),polysaccharides, polylactic acid, polyglycolic acid, polycaproic acid,polybutyric acid, polyvaleric acid, and copolymers, polymer alloys,polymer mixtures, and combinations thereof.

[0063] A marker 24 typically should remain in place and detectablewithin a patient for up to at least 2 weeks to have practical clinicalvalue. Thus, a marker 24, including a plug 26 configured to serve as amarker, is detectable at a biopsy site within a patient for a timeperiod of at least 2 weeks, preferably at least about 6 weeks, and mayremain detectable for a time period of up to about 20 weeks, morepreferably for a time period of up to about 12 weeks. In someembodiments, a marker material for use in markers 24 and plugs 26embodying features of the invention is preferably not detectable about 6months after placement at a biopsy site, and is more preferably notdetectable with ultrasound about 12 weeks after placement at a biopsysite. Thus, a preferable in-vivo lifetime for a marker material for usein markers 24 and plugs 26 having features of the invention is betweenabout 6 weeks and about 12 weeks.

[0064] In embodiments of the invention, a marker 24, and a plug 26configured to serve as a marker 24 following expulsion from a deliverytube 14, may be detectable by ultrasound. Ultrasound-detectable markers24 and plugs 26 may be formed with ultrasound detectable materials, suchas stainless steel, titanium, platinum and the like, otherbio-compatible metals, ceramics, metal oxides or polymers, or compositesor mixtures of these materials. Typically, any material which reflectsultrasound energy may be suitable for use in an ultrasound-detectablemarker. For example, materials having bubbles, internal voids, orgas-filled spaces, are detectable by ultrasound. A marker 24 or a plug26 may be formed so as to include voids, such as cavities, to enhancetheir detectability by ultrasound. For example, a cavity size of betweenabout 10 microns and about 500 microns, preferably between about 50microns to about 200 microns, may be suitable to enhance theultrasound-detectability of a marker 24 or plug 26.

[0065] Plugs 26 and markers 24 are configured to fit within a bore 16 ofa delivery tube 14. A delivery tube 14 maybe configured to fit within aguide cannula 72, such as a guide cannula sized to accept a Mammotome®,Tru-Cut®, or SenoCor® biopsy device. Typically, a plug 26 or marker 24will have a diameter determined by the size of a bore 16, typicallybetween about 0.02″ (0.5 mm) and about 0.5″ (12 mm), preferably betweenabout 0.04″ (1 mm) and about 0.3″ (8 mm). In addition, a plug 26 ormarker 24 may have a length of between about 0.04″ (1 mm) and about 0.8″(20 mm), preferably between about 0.1″ (2.5 mm) and about 0.6″ (15 mm).

[0066] A radiopaque element 40 may be made with any suitable radiopaquematerial, including stainless steel, platinum, gold, iridium, tantalum,tungsten, silver, rhodium, nickel, bismuth, other radiopaque metals,alloys and oxides of these metals, barium salts, iodine salts, iodinatedmaterials, and combinations of these. Radiopaque materials and markersmay be permanent, or may be temporary and not detectable after a periodof time subsequent to their placement within a patient. MRI contrastagents such as gadolinium and gadolinium compounds, for example, arealso suitable for use with plugs 26 and/or markers 24 embodying featuresof the invention. Colorants, such as dyes (e.g., methylene blue andcarbon black) and pigments (e.g., barium sulfate), may also be includedin markers 24 and/or plugs 26 embodying features of the invention.

[0067] Markers 24, and plugs 26 configured to serve as markers, may alsoinclude other materials besides marker materials, including anestheticagents, hemostatic agents, pigments, dyes, materials detectable bymagnetic resonance imaging (MRI), inert materials, and other compounds.

[0068] In any of the above-described embodiments of the invention, aplug 26 may include an adhesive component to aid the plug 26 to adhereto a delivery tube 14. In addition, an adhesive component may be usefulto aid a marker 24 (and a plug 26 after expulsion from a delivery tube14) to adhere to adjacent tissue within the body of a patient, such asat a biopsy site. The adhesive component may comprise a biocompatibleadhesive, such as a polyurethane, polyacrylic compound,polyhydroxymethacrylate, fibrin glue (e.g., Tisseal™), collagenadhesive, or mixtures thereof.

[0069] While particular forms of the invention have been illustrated anddescribed, it will be apparent that various modifications can be madewithout departing from the spirit and scope of the invention.Accordingly, it is not intended that the invention be limited to thespecific embodiments illustrated. It is therefore intended that thisinvention be defined by the scope of the appended claims as broadly asthe prior art will permit, and in view of the specification if need be.All patents and patent applications referred to above are herebyincorporated by reference in their entirety.

What is claimed is:
 1. An intracorporeal marker delivery devicecomprising: a delivery tube which has a distal tip, a discharge orificeand an inner bore extending to the orifice; at least one marker bodywhich is slidably disposed within the bore; and a plug, which isreleasably secured within the bore distal to the marker, which isconfigured to retain said at least one marker body when secured withinthe bore, and which allows passage of a marker body out of said orificewhen released from the bore.
 2. The delivery device of claim 1, whereinsaid plug is formed at least in part of a marker.
 3. The delivery deviceof claim 1, wherein said plug at least partially occludes said orificeso as to prevent ingress of tissue.
 4. The delivery device of claim 1,wherein said plug occludes substantially all of said orifice.
 5. Thedelivery device of claim 1, wherein said plug is disposed at least inpart within said orifice.
 6. The delivery device of claim 5, wherein atleast part of said plug is configured to fit tightly within at leastpart of said bore so as to be releasably secured therein.
 7. Thedelivery device of claim 6, wherein at least part of said plug isconfigured to press against at least part of said bore.
 8. The deliverydevice of claim 7, wherein said plug comprises an expandable elementconfigured to urge against said bore.
 9. The delivery device of claim 8,wherein said expandable element is selected from the group of elementsconsisting of a spring, a coil, a clip, a loop, an arch, and a resilientcore.
 10. The delivery device of claim 9, wherein said expandableelement includes a radiopaque element.
 11. The delivery device of claim1, wherein said delivery tube has a tube wall has at least one retainingfeature configured to releasably retain a plug.
 12. The delivery deviceof claim 11, wherein a delivery tube wall retaining feature includes aprotuberance.
 13. The delivery device of claim 11, wherein a deliverytube wall retaining feature includes a recess.
 14. The delivery deviceof claim 11, wherein a delivery tube wall retaining feature is selectedfrom the group consisting of notches, holes, slots, tabs, and ridges.15. The delivery device of claim 1, wherein said plug is formed of abioresorbable material.
 16. The delivery device of claim 2, wherein saidplug comprises a permanent marker.
 17. The delivery device of claim 2,wherein said plug is detectable with ultrasound.
 18. The delivery deviceof claim 2, wherein said plug is formed at least in part of a radiopaquematerial.
 19. The delivery device of claim 2, wherein said plug has atleast one bioactive element.
 20. The delivery device of claim 19,wherein at least one bioactive element is selected from the groupconsisting of hemostatic materials, anesthetic materials, absorbentmaterials, antibiotic materials, antifungal materials, antiviralmaterials, chemotherapeutic materials, radioactive materials, and otherpharmaceutical materials.
 21. The delivery device of claim 1, wherein aplurality of markers are disposed within the bore proximal to the plug.22. The delivery device of claim 21, wherein a movable plunger isslidably disposed within the bore and is configured to expel markersthrough said orifice.
 23. A plug configured to be releasably retainedwithin a bore of a delivery device effective to retain a marker thereinand having an inclined end surface.
 24. The plug of claim 23, whereinsaid plug is formed of a bioresorbable material.
 25. The plug of claim23, wherein said plug is a permanent marker.
 26. The plug of claim 23,wherein said plug is formed of an ultrasound detectable material. 27.The plug of claim 23, wherein said plug is formed of a radiopaquematerial.
 28. The plug of claim 23, wherein said plug has at least onebioactive element.
 29. The plug of claim 28, wherein at least onebioactive element is selected from the group consisting of hemostaticmaterials, anesthetic materials, absorbent materials, antibioticmaterials, antifungal materials, antiviral materials, chemotherapeuticmaterials, radioactive materials, and other pharmaceutical materials.30. A marker delivery system comprising a delivery tube having a distaltip with an orifice therein, an inner bore extending therein to theorifice in the distal tip, a movable plunger disposed within said bore,and a plug releasably secured within the orifice within the distal tip.31. The marker delivery device of claim 30, wherein a distal portion ofsaid delivery tube wall has at least one retaining feature configured toreleasably retain the plug.
 32. The marker delivery device of claim 31,wherein said retaining feature is selected from the group consisting ofnotches, holes, slots, tabs, and ridges.
 33. A method of delivering amarker to a desired location within a body of a patient, comprisinginserting into a patient a marker delivery device comprising a deliverycannula with a distal tip and having a bore, an orifice disposed at saiddistal tip, a plug releasably retained within the bore, and at least onemarker slidably disposed within the bore proximal to the plug; advancinga plunger within the bore to press on a marker therein against the plugthereby; and expelling the plug and a marker from said orifice into saiddesired location.
 34. The method of claim 33, wherein insertingcomprises guiding said delivery cannula within said body of said patientwith the aid of a guide cannula.
 35. The method of claim 33, wherein thedelivery cannula is guided within the patient with the aid of an imagingdevice.
 36. The method of claim 35, wherein said imaging device is anultrasound imaging device.
 37. The method of claim 35, wherein saidimaging device is an x-ray imaging device.
 38. The method of claim 35,wherein said imaging device is a magnetic resonance imaging device. 39.The method of claim 33, wherein the desired location is a lesion sitewithin said body of said patient.
 40. The method of claim 33, whereinthe desired location is a biopsy cavity within said body of saidpatient.
 41. The method of claim 39, wherein inserting further comprisesguiding said delivery cannula adjacent said lesion site with the aid ofan imaging device.
 42. The method of claim 40, wherein inserting furthercomprises guiding said delivery cannula adjacent said biopsy cavity withthe aid of an imaging device.
 43. An intracorporeal marker deliverydevice comprising: a delivery tube which has a distal tip, a dischargeorifice and an inner bore extending to the orifice; and a plugcomprising a marker body which is releasably secured within the bore anddisposed so as to at least partially occlude said discharge orifice. 44.The intracorporeal marker delivery device of claim 43, wherein said plugcomprises a bioresorbable marker.
 45. The intracorporeal marker deliverydevice of claim 43, wherein said plug comprises a permanent marker. 46.The intracorporeal marker delivery device of claim 43, wherein said plugcomprises a radiopaque element.
 47. The intracorporeal marker deliverydevice of claim 43, wherein said plug is detectable with ultrasound. 48.The intracorporeal marker delivery device of claim 43, wherein said plugcomprises a bioactive element.
 49. The intracorporeal marker deliverydevice of claim 48, wherein said plug comprises a bioactive elementselected from the group consisting of hemostatic materials, anestheticmaterials, absorbent materials, antibiotic materials, antifungalmaterials, antiviral materials, chemotherapeutic materials, radioactivematerials, and other pharmaceutical materials.